Systemic lupus erythematosus
Conditions
Interventions
Experimental group:PIT565 monotherapy
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Signed informed consent must be obtained prior to participation in the study; 2.Male and female patients, aged 18 to 75 years at screening, diagnosed with SLE according to the 2019 ACR/EULAR criteria (Aringer et al 2019) at least 24 weeks prior to screening; 3.Documentation of one or more of the following SLE autoantibodies measured at any time prior to screening: ANA (greater than or equal to 1:80); OR anti dsDNA above the upper limit of normal (ULN); OR anti-Sm above the ULN; 4.Active SLE disease, as demonstrated at screening by a SLEDAI-2K >= 6 and/or a SLEDAI-2K>= 4 with at least one clinical criterion; 5.Failure to respond (i.e., having active disease as described above despite treatment) to the following classes of therapies for the treatment of SLE: oral glucocorticoids and antimalarial agents, and/or at least one immunosuppressant (including methotrexate, azathioprine, mycophenolate, cyclophosphamide or calcineurin inhibitors) and/or at least one biologic (including belimumab, anifrolumab, or rituximab), unless contra-indicated or discontinued due to intolerance or toxicity; 6.Immunization against pneumococcus, influenza, and COVID/19 infection at least 2 weeks prior to first dosing; 7.Able to communicate well with the investigator, to understand the study and willing to comply with the requirements of the study (e.g. lifestyle considerations as defined in Section 5.3);
Exclusion criteria
Exclusion criteria: 1.Severe SLE-related organ damage or life-threatening disease at screening; 2.Any acute, severe lupus-related flare during screening that needs immediate treatment such as acute CNS lupus (e.g., psychosis, epilepsy) or catastrophic antiphospholipid syndrome; 3.Presence of severe lupus kidney disease as defined by worsening proteinuria or estimated glomerular filtration rate (eGFR), which in the opinion of the Investigator requires immunesuppressive induction or maintenance treatment at screening; 4. Use of the following prohibited drugs: (1) Receipt of any anti-CD19 or anti-CD20 therapy or any B cell-depleting therapy, such as berinatumumab, rituximab, olizumab, or obatumumab, within 6 months before or during screening; (2) Glucocorticoids at a dose of > 30 mg of prednisone equivalent per day during the 4 weeks before the first dose (or stable doses of = 4 weeks before the first dose). This did not apply to premedication (dexamethasone 16 mg or prednisone 100 mg). (3) Use of cyclophosphamide within 2 months before or during screening; (4) JAK, Bruton tyrosine kinase, or tyrosine kinase 2 inhibitors, including baritinib, tofacitinib, upadacitinib, non-goatinib, ibrutinib, or finerbrutinib, administered within 4 weeks before or during screening; (5) Receipt of any biologic therapy within 2 months before or during screening, including but not limited to belimumab, anilumab, ustekinumab, secukinumab, or acercept; (6) Vaccination with any live or attenuated vaccine within 2 months before dose; (7) IVIG infusion for infection prophylaxis within 14 days before study treatment and up to 6 weeks after the last dose; 5. Any of the following heart diseases (1) Unstable angina, myocardial infarction, coronary-artery bypass grafting (CABG), or stroke within 6 months before screening (2) Clinically significant and/or uncontrolled heart disease (e.g., congestive heart failure requiring treatment (NYHA >= 2), uncontrolled hypertension; 6. Any of the following arrhythmias or ECG abnormalities: (1) Clinically significant arrhythmias such as sustained ventricular tachycardia and clinically significant second - or third-degree atrioventricular block without a pacemaker (2) Family history of long QT syndrome or known torsades de pointes (3) Resting QTcF >=450 ms (men) or >=460 ms (women) at screening (4) Use of medications known to prolong the QT interval, unless they can be permanently discontinued during the study; 7. Patients with the following laboratory values at screening: (1) Creatinine clearance = 45 mL/min calculated by Cockcroft-Gault formula (or similar institutional standards) (2) aspartate aminotransferase (AST) > 3.0 × ULN (3) ALT > 3.0 × ULN (4) Total bilirubin > 1.5 × ULN (for Gilbert's syndrome patients, if their total bilirubin > 3.0 × ULN and direct bilirubin > 1.5 × ULN, they are excluded) (5) Absolute neutrophil count < 1.0 × 10^9/L (6) platelet count < 50 × 10^9/L (7) hemoglobin < 8 g/dL (8) B cell count < 10 cells /µL; 8.Initiation of hematopoietic colony-stimulating growth factors (e.g., G-CSF, M-CSF), thrombopoietin mimetics or erythroid stimulating agents <= 2 weeks prior to study treatment. If thrombopoietin mimetics or erythroid stimulating agents were initiated more than 2 weeks prior to study treatment and the patient is on a stable dose, they can be maintained. GMCSF is not permitted due to the possible exacerbation of CRS; 9.Use of othe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Existence/non existence of adverse events (AEs) and treatment-related AEs;Changes in vital signs, laboratory parameters, and ECG evaluation compared to baseline;Existence/non existence of dose limiting toxicity (DLT);Existence/non existence of serious adverse events (SAEs); | — |
Secondary
| Measure | Time frame |
|---|---|
| At baseline and with/without the presence of anti drug antibodies (ADA) over time;Serum concentration of PIT565 and derived PK parameters (such as Cmax, AUC); | — |
Countries
China
Contacts
Public ContactMen Taoli
Peking Union Medical College Hospital
Outcome results
None listed